Neurokinin-1 receptor antagonist orvepitant is an effective inhibitor of itch-associated response in a Mongolian gerbil model of scratching behaviour.

Data suggest that substance P could play an important role in pruritus, and therefore, blockade of the neurokinin (NK)-1 receptor might be antipruritic. Thus, we explored in the Mongolian gerbil the effect on scratching behaviour, induced by intra-dermal injection of the NK-1 receptor-specific agonist GR73632, of oral administration of the NK-1 receptor antagonist orvepitant. Orvepitant at all doses tested (0.

Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.

The last two decades have provided a large weight of preclinical data implicating the neurokinin-1 receptor (NK1) and its cognate ligand substance P (SP) in a broad range of both central and peripheral disease conditions. However, to date, only the NK1 receptor antagonist aprepitant has been approved as a therapeutic and this is to prevent chemotherapy-induced nausea & vomiting (CINV). The belief remained that the full therapeutic potential of NK1 receptor antagonists had yet to be realized; therefore clinical evidence that NK1 receptor antagonists may be effective in major depression disorder, resulted in a significant further investment in discovering novel CNS penetrant druggable NK1 receptor antagonists to address this condition.

Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies.

Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD).

Gene selection in arthritis classification with large-scale microarray expression profiles.

The use of large-scale microarray expression profiling to identify predictors of disease class has become of major interest. Beyond their impact in the clinical setting (i.e.